Abstract
Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C(MMC), halofuginone (Hal), and transforming growth factor β3 (TGF-β3) exhibits antiscarring effects that may prevent post-ESD stricture formation. Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n=6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5mg (n=2), 0.5mg (n=2); Hal 5mg (n=2), 1.5mg (n=2), 0.5mg (n=2); TGF-β3 2μg (n=2), 0.5μg (n=2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80% or the animals were unable to maintain weight. The control group had a luminal diameter reduction of 78.2±10.9% by 2weeks and were euthanized by week 3. Compared at 2weeks, the Hal group showed a decrease in mean stricture formation (68.4% low dose, 57.7% high dose), while both TGF-β3 dosage groups showed no significant change (65.3% low dose, 76.2% high dose). MMC was most effective in stricture prevention (53.6% low dose, 35% high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-β3 and Hal treated areas appeared re-epithelialized and healthy. Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formationafter EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy.
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